Investigation of dosimetric characteristics of radiochromic film in response to alpha particles emitted from Americium-241.

BACKGROUND: In radiotherapy, it is essential to deliver prescribed doses to tumors while minimizing damage to surrounding healthy tissue. Accurate measurements of absorbed dose are required for this purpose. Gafchromic® external beam therapy (EBT) radiochromic films have been widely used in radiotherapy. While the dosimetric characteristics of the EBT3 model film have been extensively studied for photon and charged particle beams (protons, electrons, and carbon ions), little research has been done on α $\alpha$ -particle dosimetry. α $\alpha$ -emitting radionuclides have gained popularity in cancer treatment due to their high linear energy transfer, short range in tissue, and ability to spare surrounding organs at risk, thereby delivering a more localized dose distribution to the tumor. Therefore, a dose-calibration film protocol for α $\alpha$ -particles is required. PURPOSE: This study aimed to develop a dose-calibration protocol for the α $\alpha$ -particle emitting radionuclide 241Am, using Monte Carlo (MC) simulations and measurements with unlaminated EBT3 films. METHODS: In this study, a MC-based user code was developed using the Geant4 simulation toolkit to model and simulate an 241Am source and an unlaminated EBT3 film. Two simulations were performed: one with voxelized geometries of the EBT3 active volume composition and the other using water. The dose rate was calculated within a region of interest in the voxelized geometries. Unlaminated EBT3 film pieces were irradiated with the 241Am source at various exposure times inside a black box. Film irradiations were compared to a 6-MV photon beam from a Varian TrueBeam machine. The simulated dose rate was used to convert the exposure times into absorbed doses to water, describing a radiochromic-film-based reference dosimetry protocol for α $\alpha$ -particles. The irradiated films were scanned and through an in-house Python script, the normalized pixel values from the green-color channel of scanned film images were analyzed. RESULTS: The 241Am energy spectra obtained from the simulations were in good agreement with IAEA and NIST databases, having differences < $<$ 0.516% for the emitted γ $\gamma$ -rays and produced characteristic x-rays and < $<$ 0.006% for the α $\alpha$ -particles. Due to the short range of α $\alpha$ -particles, there was no energy deposition in the voxels outside the active 241Am source region projected onto the film surface. Thus, the total dose rate within the voxels covering the source was 0.847 ± $\pm$ 0.003 Gy/min within the sensitive layer of the film (LiPCDA) and 0.847 ± $\pm$ 0.004 Gy/min in water, indicating that the active volume can be considered water equivalent for the 241Am beam quality. A novel approach was employed in α $\alpha$ -film dosimetry using an exponential fit for the green channel, which showed promising results by reducing the uncertainty in dose estimation within 5%. Although the statistical analysis did not reveal significant differences between the 6-MV photon beam and the α $\alpha$ calibration curves, the dose-response curves exhibited the expected behavior. CONCLUSIONS: The developed MC user code simulated the experimental setup for α $\alpha$ -dosimetry using radiochromic film with acceptable uncertainty. Unlaminated EBT3 film is suitable for the dosimetry of α $\alpha$ -radiation at low doses and can be used in conjunction with other unlaminated GafChromic® films for quality assurance and research purposes.

Physical wedge as a tool for radiochromic film calibration.

Reliable calibration is one of the major challenges in using radiochromic films (RCF) for radiation dosimetry. In this study the feasibility of using dose gradients produced by a physical wedge (PW) for RCF calibration was investigated. The aim was to establish an efficient and reproducible method for calibrating RCF using a PW. Film strips were used to capture the wedge dose profile for five different exposures and the acquired scans were processed to generate corresponding net optical density wedge profiles. The proposed method was compared to the benchmark calibration, following the guidelines for precise calibration using uniform dose fields. The results of the benchmark comparison presented in this paper showed that using a single film strip for measuring wedge dose profile is sufficient for estimating a reliable calibration curve within the recorded dose range. Furthermore, the PW calibration can be extrapolated or extended by using multiple gradients for the optimal coverage of the desired calibration dose range. The method outlined in this paper can be readily replicated using the equipment and expertise commonly found in a radiotherapy center. Once the dose profile and central axis attenuation coefficient of the PW are determined, they can serve as a reference for a variety of calibrations using different types and batches of film. This investigation demonstrated that the calibration curves obtained with the presented PW calibration method are within the bounds of the measurement uncertainty evaluated for the conventional uniform dose field calibration method.

Image-Guided Brachytherapy for Rectal Cancer: Reviewing the Past Two Decades of Clinical Investigation.

(1) Background: The introduction of total mesorectal excision (TME) for rectal cancer has led to improvement in local recurrence (LR) outcomes. Furthermore, the addition of preoperative external beam radiotherapy to TME reduces LR to less than 6%. As a trade-off to these gradual improvements in local therapies, the oncology community's work is now focusing on mitigating treatment-related toxicities. In other words, if a small proportion of 4-6% of rectal cancer patients benefit from additional local therapy beyond TME, the burden of acute and long-term side effects must be considered with care. (2) Methods: With the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy. The treatment concept was tested in phase I and II studies: first in the pre-operative setting, and then as a boost after external beam radiation therapy, as a dose-escalation study, to achieve higher local tumor control. (3) Results: HDREBT is safe and effective in achieving a high tumor regression rate and was well tolerated in a phase II multicenter and two matched-pair studies. (4) Conclusions: HDREBT is a conformed radiation therapy that is safe and effective, and is presently explored in a phase III dose-escalation study in the NOM of patients with operable rectal cancer.

MORPHEUS Phase II-III Study: A Pre-Planned Interim Safety Analysis and Preliminary Results.

BACKGROUND: We explored image-guided adaptive endorectal brachytherapy patients electing non-operative management for rectal cancer. We present the first pre-planned interim analysis. METHODS: In this open-label phase II-III randomized study, patients with operable cT2-3ab N0 M0 rectal cancer received 45 Gy in 25 fractions of pelvic external beam radiotherapy (EBRT) with 5-FU/Capecitabine. They were randomized 1:1 to receive either an EBRT boost of 9 Gy in 5 fractions (Arm A) or three weekly adaptive brachytherapy (IGAEBT) boosts totaling 30 Gy (Arm B). Patient characteristics and toxicity are presented using descriptive analyses; TME-free survival between arms with the intention to treat the population is explored using the Kaplan-Meier method. RESULTS: A total of 40 patients were in this analysis. Baseline characteristics were balanced; acute toxicities were similar. Complete clinical response (cCR) was 50% (n = 10/20) in Arm A and 90% in Arm B (n = 18/20). Median follow-up was 1.3 years; 2-year TME-free survival was 38.6% (95% CI: 16.5-60.6%) in the EBRT arm and 76.6% (95% CI: 56.1-97.1%) in the IGAEBT arm. CONCLUSIONS: Radiation intensification with IGAEBT is feasible. This interim analysis suggests an improvement in TME-free survival when comparing IGAEBT with EBRT, pending confirmation upon completion of this trial.

Clinical Implication of Dosimetry Formalisms for Electronic Low-Energy Photon Intraoperative Radiation Therapy.

PURPOSE: Intraoperative radiation therapy (IORT) using the INTRABEAM, a miniature x-ray source, has shown to be effective in treating breast cancer. However, recent investigations have suggested a significant deviation between the reported and delivered doses. In this work, the dose delivered by INTRABEAM in the TARGIT breast protocol was investigated, along with the dose from the Xoft Axxent, another source used in breast IORT. METHODS AND MATERIALS: The absorbed dose from the INTRABEAM was determined from ionization chamber measurements using: (a) the manufacturer-recommended formula (Zeiss V4.0 method), (b) a Monte Carlo calculated chamber conversion factor (CQ method), and (c) the formula consistent with the TARGIT breast protocol (TARGIT method). The dose from the Xoft Axxent was determined from ionization chamber measurements using the Zeiss V4.0 method and calculated using the American Association of Physicists in Medicine TG-43 formalism. RESULTS: For a nominal TARGIT prescription of 20 Gy, the dose at the INTRABEAM applicator surface ranged from 25.2 to 31.7 Gy according to the CQ method for the largest (5 cm) and smallest (1.5 cm) diameter applicator, respectively. The Zeiss V4.0 method results were 7% to 10% lower (23.2 to 28.6 Gy). At 1 cm depth, the CQ and Zeiss V4.0 absorbed doses were also larger than those predicted by the TARGIT method. The dose at 1 cm depth from the Xoft Axxent for a surface dose of 20 Gy was slightly less than INTRABEAM (3%-7% compared with CQ method). An exception was for the 3 cm applicator, where the Xoft dose was appreciably lower (31%). CONCLUSIONS: The doses delivered in the TARGIT breast protocol with INTRABEAM were significantly greater than the prescribed 20 Gy and depended on the size of spherical applicator used. Breast IORT treatments with the Xoft Axxent received less dose compared with TARGIT INTRABEAM, which could have implications for studies comparing clinical outcomes between the 2 devices.

Positional and angular tracking of HDR 192 Ir source for brachytherapy quality assurance using radiochromic film dosimetry.

PURPOSE: To quantify and verify the dosimetric impact of high-dose rate (HDR) source positional uncertainty in brachytherapy, and to introduce a model for three-dimensional (3D) position tracking of the HDR source based on a two-dimensional (2D) measurement. This model has been utilized for the development of a comprehensive source quality assurance (QA) method using radiochromic film (RCF) dosimetry including assessment of different digitization uncertainties. METHODS: An algorithm was developed and verified to generate 2D dose maps of the mHDR-V2 192 Ir source (Elekta, Veenendaal, Netherlands) based on the AAPM TG-43 formalism. The limits of the dosimetric error associated with source (0.9 mm diameter) positional uncertainty were evaluated and experimentally verified with EBT3 film measurements for 6F (2.0 mm diameter) and 4F (1.3 mm diameter) size catheters at the surface (4F, 6F) and 10 mm further (4F only). To quantify this uncertainty, a source tracking model was developed to incorporate the unique geometric features of all isodose lines (IDLs) within any given 2D dose map away from the source. The tracking model normalized the dose map to its maximum, then quantified the IDLs using blob analysis based on features such as area, perimeter, weighted centroid, elliptic orientation, and circularity. The Pearson correlation coefficients (PCCs) between these features and source coordinates (x, y, z, θy , θz ) were calculated. To experimentally verify the accuracy of the tracking model, EBT3 film pieces were positioned within a Solid Water® (SW) phantom above and below the source and they were exposed simultaneously. RESULTS: The maximum measured dosimetric variations on the 6F and 4F catheter surfaces were 39.8% and 36.1%, respectively. At 10 mm further, the variation reduced to 2.6% for the 4F catheter which is in agreement with the calculations. The source center (x, y) was strongly correlated with the low IDL-weighted centroid (PCC = 0.99), while the distance to source (z) was correlated with the IDL areas (PCC = 0.96) and perimeters (PCC = 0.99). The source orientation θy was correlated with the difference between high and low IDL-weighted centroids (PCC = 0.98), while θz was correlated with the elliptic orientation of the 60-90% IDLs (PCC = 0.97) for a maximum distance of z = 5 mm. Beyond 5 mm, IDL circularity was significant, therefore limiting the determination of θz (PCC ≤ 0.48). The measured positional errors from the film sets above and below the source indicated a source position at the bottom of the catheter (-0.24 ± 0.07 mm). CONCLUSIONS: Isodose line features of a 2D dose map away from the HDR source can reveal its spatial coordinates. RCF was shown to be a suitable dosimeter for source tracking and dosimetry. This technique offers a novel source QA method and has the potential to be used for QA of commercial and customized applicators.

Dose measurements nearby low energy electronic brachytherapy sources using radiochromic film.

PURPOSE: We investigate the effect of the GafChromic™ film EBT3 model absorbed dose energy response when used for dose measurements around low-energy photon sources. Monte Carlo based correction procedure in synergy with appropriate calibration curves was shown to provide more accurate absorbed dose (either relative or absolute). An assessment was made of possible dose errors that might be encountered if such energy dependent response is ignored. METHODS: We measured PDDs in water from a Xoft 50 kVp source using EBT3 film, and compared to PDD measurements acquired with a PTW-TN34013 parallel-plate ionization chamber. For the x-ray source, we simulated spectra using the EGSnrc (BEAMnrc) Monte Carlo code, and calculated Half Value Layer (HVL) at different distances from the source in water. Measurement strips of EBT3 film were positioned at distances of 2-6 cm from the Xoft source in a water phantom using a custom-made holder and irradiated simultaneously. RESULTS: Our results show that film calibration curves obtained at beam qualities near the effective energy of the Xoft 50 kVp source in water lead to variation in absorbed dose energy dependence of the response of around 5%. However, if the calibration curve was established in an MV beam quality, the error in absorbed dose could be as large as 20%. CONCLUSION: Accurate dose measurements using radiochromic films at low photon energies require that the radiochromic film dosimetry system be calibrated at appropriate corresponding low energies, as large absorbed dose errors are expected when film calibration is performed in MV beam qualities.

Image Guided Adaptive Endorectal Brachytherapy in the Nonoperative Management of Patients With Rectal Cancer.

PURPOSE: Organ preservation or nonoperative management of rectal cancer is of growing interest. Image guided adaptive endorectal brachytherapy is a radiation dose escalation modality: we explored its role in elderly patients unfit for surgery and patients refusing surgery. METHODS AND MATERIALS: In this registry study, patients with rectal cancer who were ineligible for surgery received 40 Gy in 16 fractions of pelvic external beam radiation therapy. They subsequently received 3 weekly image guided adaptive brachytherapy boosts of 10 Gy to the residual tumor, for a total of 30 Gy in 3 fractions. Complete clinical response (cCR) and local control were the primary endpoints. RESULTS: 94 patients were included; the median age was 81.1 years. With a median follow-up of 1.9 years, the proportion of cCR was 86.2%, the tumor regrowth proportion was 13.6%, and the cumulative incidence of local relapse was 2.7% at 1 year and 16.8% at 2 years. When considering responders and nonresponders, the 2-year local control was 71.5%. The overall survival at 2 years was 63.6%. Acute rectal grade 1 to 2 toxicity included all patients: 12.8% of patients had late bleeding requiring iron replacement, blood transfusions, or argon plasma therapy. CONCLUSIONS: Results of this registry study, evaluating radiation dose escalation for elderly medically unfit patients with unselected tumors, reveal that a high proportion of patients achieved cCR with a manageable toxicity profile. This technology will likely contribute to the challenging nonoperative management paradigm of rectal cancer.

Modeling the primary source intensity distribution: reconstruction and inter-comparison of six Varian TrueBeam sources.

The primary source size is one of the most important beam model parameters in small photon fields. In this work we apply a recently suggested reconstruction technique to characterize the primary source of 6 Varian TrueBeam (TB) linacs. A series of photon fluence profile measurements were performed on 6 Varian TB linacs in the crossplane and inplane orientation using radiochromic film in air and a 2 mm Pb foil as a build-up layer. An image reconstruction algorithm was then applied, based on the maximum likelihood expectation-maximization (MLEM) algorithm, to estimate the source distribution. The method iteratively ray-traces photons from the source plane to the measurement plane to extract source profile corrections. The technique was first benchmarked using a Monte Carlo (MC) model of a Varian TrueBeam with known input Gaussian source sizes. The robustness of the suggested technique was also tested by randomly sampling different combinations of source and field size values and repeating the reconstruction. At the MC benchmarking stage the MLEM reconstruction algorithm was capable of reproducing the Gaussian shape with a RMSE less than 4.0%, while the reconstructed source size (FWHM) and field size were determined with an accuracy level of 0.14 mm and 0.10 mm respectively. Experimentally, the reconstructed TB sources presented FWHM values between 1.02-1.5 mm ([Formula: see text]-0.18 mm) and 1.08-1.42 mm ([Formula: see text]-0.13 mm) in the crossplane and inplane orientations respectively. All TB sources studied in this work can be considered symmetric within uncertainties with the exception of one. The source distribution presented systematic deviations from a Gaussian distribution mostly in the lower tail region. Multi-parameter functional forms, such as Pearson VII or double Gaussian presented improvements in modeling the source in this region, but increase the model complexity. The reconstructed sources measured in this work can serve as reference values for commissioning beam models in small fields and set upper and lower thresholds values of the expected source size for a TB linac.

Optimization of HDRBT boost dose delivery for patients with rectal cancer.

PURPOSE: We describe methods to improve dose delivery for patients with rectal cancer receiving boost brachytherapy after external beam radiotherapy. METHODS AND MATERIALS: Patients with rectal cancer who were ineligible or refusing surgery are treated with external beam radiotherapy and subsequently with three weekly image-guided volume-adapted high-dose-rate brachytherapy boosts of 10 Gy to the residual clinical target volume, for a total of 30 Gy in three fractions. Tungsten shielding placed at the center of intracavitary mold applicator and double-balloon technique was used to improve dose conformity to the target. RESULTS: Our results show that the use of tungsten shield and double balloon reduces the dose gradient within the target volume to receive the prescription boost dose of 10 Gy from maximum dose of 60 Gy down to 20 Gy. CONCLUSIONS: We outlined two methods for achieving higher high-dose-rate brachytherapy dose conformity using the tungsten shielding rods (to spare contralateral healthy tissues) and double-balloon technique (to decrease dose gradient within the target to minimize dose to the proximal mucosa).

Image quality for radiotherapy CT simulators with different scanner bore size.

PURPOSE: We compare image quality parameters derived from phantom images taken on three commercially available radiotherapy CT simulators. To make an unbiased evaluation, we assured images were obtained with the same surface dose measured using XR-QA2 model GafChromic™ film placed at the imaging phantom surface for all three CT-simulators. METHODS: Radiotherapy CT simulators GE LS 16, Philips Brilliance Big Bore, and Toshiba Aquilion LB were compared in terms of spatial resolution, low contrast detectability, image uniformity, and contrast to noise ratio using CATPHAN-504 phantom, scanned with Head and Pelvis protocols. Dose was measured at phantom surface, with CT scans repeated until doses on all scanners were within 2%. RESULTS: In terms of spatial resolution, the GE simulator appears slightly better, while Philips CT images are superior in terms of SNR for both scanning protocols. The CNR results show that Philips CT images appear to be better, except for high Z material, while Toshiba appears to fit in between the two simulators. CONCLUSIONS: While the image quality parameters for three RT CT simulators show comparable results, the scanner bore size is of vital importance in various radiotherapy applications. Since the image quality is a function of a large number of confounding parameters, any loss in image quality due to scanner bore size could be compensated by the appropriate choice of scanning parameters, including the exposure and by balancing between the additional imaging dose to the patient and high image quality required in highly conformal RT techniques.

Physics aspects of the Papillon technique-Five decades later.

PURPOSE: The Papillon technique using 50-kVp soft X-rays to treat rectal adenocarcinomas was developed and clinically implemented in the 1960s. We describe differences between accurate dosimetry and clinical implementation of this technique that is extending from its very inception to date. METHODS AND MATERIALS: A renaissance of the Papillon technique occurred with two recently introduced 50-kVp systems: Papillon+ by Ariane and a custom-made rectal applicator (consisting of a surface applicator inserted into a proctoscope) by iCAD's Xoft Axxent Electronic Brachytherapy (eBT) System (iCad, Inc., Sunnyvale, CA). In contrast to the initial design, we investigated the impact of introducing a plastic lid, which would provide more reproducible and more accurate dose delivery across the rectal adenocarcinoma patient population. We use both parallel-plate chamber and radiochromic film dosimeters to determine differences in basic dosimetry characteristics (beam half-value layers, outputs, percent depth doses, and profiles) between the Xoft Electronic Brachytherapy rectal applicator system with and without the plastic lid in place. RESULTS: Compared to the open-cone applicator, the proposed applicator with the plastic lid produces a slightly harder (more penetrating) beam quality (half-value layer of 1.4 vs. 1.3-mm Al), but with reduced output (by 33%), and a slightly broader beam with flatness not worse than 3% and symmetry not worse than 2%. CONCLUSIONS: In addition to characterizing beam properties modified by the possible introduction of the plastic cap, we also pointed out and addressed misconceptions in the use of radiochromic films for dose measurements at low-energy photon beams.

Dose comparison between TG-43-based calculations and radiochromic film measurements of the Freiburg flap applicator used for high-dose-rate brachytherapy treatments of skin lesions.

PURPOSE: Current high-dose-rate brachytherapy skin treatments with the Freiburg flap (FF) applicator are planned with treatment planning systems based on the American Association of Physicists in Medicine TG-43 data sets, which assume full backscatter conditions in dose calculations. The aim of this work is to describe an experimental method based on radiochromic film dosimetry to evaluate dose calculation accuracy during surface treatments with the FF applicator at different depths and bolus thicknesses. METHODS AND MATERIALS: Absolute doses were measured using a reference EBT3 radiochromic film dosimetry system within a Solid Water phantom at different depths (0, 0.5, 1, 2, and 3 cm) with respect to the phantom surface. The impact of bolus (up to 3-cm thickness) placed on top of the applicator was investigated for two clinical loadings created using Oncentra MasterPlan: 5 cm × 5 cm and 11 cm × 11 cm. RESULTS: For smaller loading and depths beyond 2 cm and for larger loading and depths beyond 1 cm, the dose difference was less than 3% (±4%). At shallower depths, differences of up to 6% (±4%) at the surface were observed if no bolus was added. The addition of 2-cm bolus for the smaller loading and 1 cm for larger loading minimized the difference to less than 3% (±4%). CONCLUSIONS: For typical FF applicator loading sizes, the actual measured dose was 6% (±4%) lower at the skin level when compared with TG-43. Additional bolus above the FF was shown to decrease the dose difference. The consideration of change in clinical practice should be carefully investigated in light of clinical reference data.

Commissioning of applicator-guided stereotactic body radiation therapy boost with high-dose-rate brachytherapy for advanced cervical cancer using radiochromic film dosimetry.

PURPOSE: To describe an EBT3 GAFCHROMIC film-based dosimetry method to be used in commissioning of a combined HDR brachytherapy (HDRB) and stereotactic body radiation therapy (SBRT) boost for treatment of advanced cervical cancer involving extensive residual disease after external beam treatment. METHODS AND MATERIALS: A cube phantom was designed to firmly fit an intrauterine tandem applicator and EBT3 radiochromic film pieces. A high-risk clinical target volume (CTVHR, Total) was contoured with an extended arm at one side. The HDRB treatment was planned to cover the proximal CTVHR, Total with 7 Gy and the distal volume, referred to as CTVHR, Distal, was planned by SBRT for dose augmentation. After HDRB treatment delivery, SBRT treatment was delivered within 1 hour by image guidance using the applicator geometry. Intentional 1D and 2D misalignments were introduced to evaluate the effect on target volumes. In addition, effect of film reirradiation at different time gaps and dose levels was evaluated. RESULTS: Film dosimetric accuracy, with up to 2 hours gap between irradiations, was shown to be unaffected. A 2%/2 mm gamma analysis between measured and planned doses showed agreement of >99%. Misalignments of more than 2 mm between applicator and SBRT isocenter resulted in suboptimal dose-volume histogram affecting mostly D98% and D90% of CTVHR, Distal. CONCLUSIONS: Visualizing how target dose-volume metrics are affected by minor misalignments between SBRT and HDRB dose gradients, in light of achievable phantom-based experimental quality assurance level, encourages the clinical applicability of this technique. Radiochromic film was shown to be a valuable tool to commission procedures combining two different treatment planning systems and modalities with varying dose rates and energy ranges.

Dual-Energy CT: Balance Between Iodine Attenuation and Artifact Reduction for the Evaluation of Head and Neck Cancer.

OBJECTIVE: Dual-energy computed tomography high energy virtual monochromatic images (VMIs) can reduce artifact but suppress iodine attenuation in enhancing tumor. We investigated this trade-off to identify VMI(s) that strike the best balance between iodine detection and artifact reduction. METHODS: The study was performed using an Alderson radiation therapy phantom. Different iodine solutions (based on estimated tumor iodine content in situ using dual-energy computed tomography material decomposition) and different dental fillings were investigated. Spectral attenuation curves and quality index (QI: 1/SD) were evaluated. RESULTS: The relationship between iodine attenuation and QI depends on artifact severity and iodine concentration. For low to average concentration solutions degraded by mild to moderate artifact, the iodine attenuation and QI curves crossed at 95 keV. CONCLUSIONS: High energy VMIs less than 100 keV can achieve modest artifact reduction while preserving sufficient iodine attenuation and could represent a useful additional reconstruction for evaluation of head and neck cancer.

New normoxic N-(Hydroxymethyl)acrylamide based polymer gel for 3D dosimetry in radiation therapy.

A novel composition of normoxic polymer gel dosimeters based on radiation-induced polymerization of N-(Hydroxymethyl)acrylamide (NHMA) is introduced in this study for 3D dosimetry for Quality Assurance (QA) in radiation therapy. Dosimeters were irradiated by 6, 10 and 18MV photon beams of a medical linear accelerator at various dose rates to doses of up to 20Gy. The dose response of polymer gel dosimeters was studied using nuclear magnetic resonance (NMR) spin-spin relaxation rate (R2) of hydrogen protons within the water molecule. Also, we measured gel response using absorption spectroscopy and found that this novel gel can be successfully utilized for both MRI- and OCT- (Optical Computed Tomography) based 3D dosimetry. We investigated dosimetric properties of six different compositions of the new NHMA-based gel in terms of dose rate, radiation beam quality and stability of dose-dependent polymerization after irradiation. We found no significant effects of these parameters on the novel gel dosimeter performance in both relaxation rate and absorbance measurements.

Warburg Effect - a Consequence or the Cause of Carcinogenesis?

Ever since its discovery (1924) the Warburg effect (aerobic glycolysis) remains an unresolved puzzle: why the aggressive cancer cells "prefer" to use the energetically highly inefficient method of burning the glucose at the cellular level? While in the course of the last 90 years several hypotheses have been suggested, to this date there is no clear explanation of this rather unusual effect. Even though it is commonly assumed that Warburg effect is a consequence of carcinogenesis, yet another hypothesis could be brought up that the cellular switch to aerobic glycolysis may represent the very point in time when a normal cell becomes cancerous. Furthermore, this switch may happen at the point where the fate of pyruvic acid is determined, caused by the inadequate supply of enzymes that promote citric as opposed to lactic acid cycle. Currently, few clinical observations, like low cancer incidence in Type 1 diabetes mellitus and increased cancer incidence in people on high carbohydrate diets might be called upon to support such hypothesis.

Reference radiochromic film dosimetry: Review of technical aspects.

For decades, film was used as a powerful two-dimensional (2D) dosimetry tool for radiotherapy treatment verification and quality assurance. Unlike the old silver-halide based radiographic films, radiochromic films change its color upon irradiation without the need for chemical development. Radiation dose deposited within a sensitive layer of the radiochromic film initiates polymerization of the active component, the degree of which depends on the amount of energy deposited. Response of the film to radiation is commonly expressed in terms of optical density change, which can be easily measured by any photometric device. However, a number of factors may have an impact on the signal detected by the measuring device. This review summarizes technical aspects associated with the establishment of reference radiochromic film dosimetry and its subsequent use for either clinical or research applications.

FDG-PET-based differential uptake volume histograms: a possible approach towards definition of biological target volumes.

OBJECTIVE: Integration of fluorine-18 fludeoxyglucose ((18)F-FDG)-positron emission tomography (PET) functional data into conventional anatomically based gross tumour volume delineation may lead to optimization of dose to biological target volumes (BTV) in radiotherapy. We describe a method for defining tumour subvolumes using (18)F-FDG-PET data, based on the decomposition of differential uptake volume histograms (dUVHs). METHODS: For 27 patients with histopathologically proven non-small-cell lung carcinoma (NSCLC), background uptake values were sampled within the healthy lung contralateral to a tumour in those image slices containing tumour and then scaled by the ratio of mass densities between the healthy lung and tumour. Signal-to-background (S/B) uptake values within volumes of interest encompassing the tumour were used to reconstruct the dUVHs. These were subsequently decomposed into the minimum number of analytical functions (in the form of differential uptake values as a function of S/B) that yielded acceptable net fits, as assessed by χ(2) values. RESULTS: Six subvolumes consistently emerged from the fitted dUVHs over the sampled volume of interest on PET images. Based on the assumption that each function used to decompose the dUVH may correspond to a single subvolume, the intersection between the two adjacent functions could be interpreted as a threshold value that differentiates them. Assuming that the first two subvolumes spread over the tumour boundary, we concentrated on four subvolumes with the highest uptake values, and their S/B thresholds [mean ± standard deviation (SD)] were 2.88 ± 0.98, 4.05 ± 1.55, 5.48 ± 2.06 and 7.34 ± 2.89 for adenocarcinoma, 3.01 ± 0.71, 4.40 ± 0.91, 5.99 ± 1.31 and 8.17 ± 2.42 for large-cell carcinoma and 4.54 ± 2.11, 6.46 ± 2.43, 8.87 ± 5.37 and 12.11 ± 7.28 for squamous cell carcinoma, respectively. CONCLUSION: (18)F-FDG-based PET data may potentially be used to identify BTV within the tumour in patients with NSCLC. Using the one-way analysis of variance statistical tests, we found a significant difference among all threshold levels among adenocarcinomas, large-cell carcinoma and squamous cell carcinomas. On the other hand, the observed significant variability in threshold values throughout the patient cohort (expressed as large SDs) can be explained as a consequence of differences in the physiological status of the tumour volume for each patient at the time of the PET/CT scan. This further suggests that patient-specific threshold values for the definition of BTVs could be determined by creation and curve fitting of dUVHs on a patient-by-patient basis. ADVANCES IN KNOWLEDGE: The method of (18)F-FDG-PET-based dUVH decomposition described in this work may lead to BTV segmentation in tumours.

Use of a control film piece in radiochromic film dosimetry.

PURPOSE: Radiochromic films change their color upon irradiation due to polymerization of the sensitive component embedded within the sensitive layer. However, agents, other than monitored radiation, can lead to a change in the color of the sensitive layer (temperature, humidity, UV light) that can be considered as a background signal and can be removed from the actual measurement by using a control film piece. In this work, we investigate the impact of the use of control film pieces on both accuracy and uncertainty of dose measured using radiochromic film based reference dosimetry protocol. METHODS: We irradiated "control" film pieces (EBT3 GafChromic(TM) film model) to known doses in a range of 0.05-1 Gy, and five film pieces of the same size to 2, 5, 10, 15 and 20 Gy, considered to be "unknown" doses. Depending on a dose range, two approaches to incorporating control film piece were investigated: signal and dose corrected method. RESULTS: For dose values greater than 10 Gy, the increase in accuracy of 3% led to uncertainty loss of 5% by using dose corrected approach. At lower doses and signals of the order of 5%, we observed an increase in accuracy of 10% with a loss of uncertainty lower than 1% by using the corrected signal approach. CONCLUSIONS: Incorporation of the signal registered by the control film piece into dose measurement analysis should be a judgment call of the user based on a tradeoff between deemed accuracy and acceptable uncertainty for a given dose measurement.